Osteoarthritis (degenerative joint disease) is the most common form of arthritis. It occurs almost universally in the aged, and is a significant medical problem in 20% of these cases. An in vivo experimental model of osteoarthritis in rabbits, and cartilage organ and cell culture systems are being utilized to further study pathogenic and pathophysiologic factors in osteoarthritis, and to compare and contrast these changes to cartilage metabolic parameters associated with normal aging. Proposed studies are designed to compare and contrast differences in metabolic activity of cartilage from different joint regions (inter and intra-articular) and at different ages, and to analyze metabolic changes associated with the developing osteoarthritic lesion. The effects of hormones, particularly estrogens and androgens, on cartilage, both in vivo and in vitro will be evaluated. Investigations relative to the isolation, purification and identification of the nature of the neutral proteoglycanase and inhibitor derived from chondrocytes in culture will be carried out. Delineation of component changes in link protein, hyaluronic acid and proteoglycan subunit will be performed to identify biochemical structural changes in the developing osteoarthritic lesion.